Each year, 1.7 million individuals sustain a TBI in the US. Between 1.6 and 3.8 million often unreported concussions occur annually, making TBI a silent epidemic of great significance. An additional one million patients are evaluated for spinal injuries every year in the US emergency departments, with 2-3 percent thereof suffering spinal cord injury. Life-saving treatment decisions for neurotrauma patients require rapid diagnosis and repeated accurate risk assessment due to evolving injury progression, as a brain trauma victim's condition typically changes each day after a TBI. Assessing moderate and severe traumatic brain and spinal cord injured patients is critical for safe urgent care, monitoring injury evolution to be ready for responding to secondary adverse events and for predicting outcome that is an early evaluation of the recovery potential for neurotrauma patients. Neurotrauma patient assessment is challenged by a broad heterogeneity in severity among patients. Identifying individual concussion victims at risk of complications, these are mild TBI patients with persistent symptoms or positive CAT scan finding, is a priority for urgent care responders as well as sports and military arena operations. Infants, children and juvenile brain injuries comprise the leading cause of death and disability in children worldwide, yet the diagnosis is challenging because signs and symptoms of TBI are absent or overlap with common childhood illnesses. Since the developing brain is more sensitive to the ionizing radiation of CAT scanning, it is imperative to reduce unnecessary CT scans by providing objective biomarker testing. In addition to the youth, the elderly are a common target group for TBI due to falls, making it desirable to distinguish TBI biomarker signals from chronic neurodegenerative marker profiles.
Diagnosis and monitoring of TBI victims is critical for assessing severity of brain disturbance and assessing the risk level accurately to respond with the appropriate preventative care. For severe TBI patients, timely surgical intervention could be life-saving. For mild TBI patients, the identification of concussion patients at risk for developing chronic pain and cognitive or psychological deficits will help to provide treatment options, guidance in coping strategies and prevent exposing the recovering brain to a second impact. Current severity evaluations rely mainly on depth and duration of coma using the Glasgow Coma Scale, which varies daily with the patient's progressive injury course and is subject to medications that may be needed to maintain a coma (Iankova, 2006). Mild TBI is evaluated by time of unconsciousness, cognitive or psychological and pain symptoms that are subjective and may be motivationally influenced. Neuroimaging tools, especially advanced modalities, are difficult to be repeatedly administered for intensive care patients and have diverse readout values that lack standardization, are not everywhere available, and are of limited use for mild TBI and pediatric patients.
Measuring blood levels of surrogate chemical biomarkers can provide a simpler, objective and more easily standardized tool as a diagnostic starting point to classify risk and needs for TBI patients. Neurotrauma biomarkers should be acutely released from traumatized brain cells, be brain and mechanical trauma specific, readily pass the blood-brain barrier and show no or consistent low levels in healthy subjects.
Currently, there is no sensitive, objective, standardized diagnostic test in clinical use for concussion patients, who are the majority of TBI patients, nor for pediatric patients with suspected TBI. These are both target populations particularly in need of objective risk assessment to prevent repeated hits putting the vulnerable brain at risk for suffering lasting brain damage. Intensive care unit head trauma patients are another target group who can benefit from repeated noninvasive blood sample analysis for monitoring, instead of, or supplementing time and cost consuming imaging because trauma progression is known for secondary deterioration on consecutive post-injury days that might require informed intervention. In addition, there remains a need for repeated biofluid sample analysis of brain injury biomarkers to determine short-term post-acute severity assessment and to determine efficacy of drug or other treatment paradigms administered to TBI patients.